8 Doxylamine Interactions You Should Know About

After several sleepless nights, you might find yourself looking for an over-the-counter (OTC) sleep aid. A common choice for occasional sleep troubles is doxylamine (Unisom SleepTabs). Doxylamine is an antihistamine found in OTC sleep aids and nighttime cold medications.

Doxylamine is generally safe and effective for many people. But it has interactions with other medications and substances you should know about. It’s always best to share a current medication list with your pharmacist and prescriber when starting something new. This can help them pinpoint potential interactions before problems arise.

Below, we’ll discuss eight notable doxylamine interactions.

Good to know: Unisom is a brand name for a line of OTC sleep aids. Not all Unisom products contain doxylamine. This article only focuses on doxylamine interactions. Contact your pharmacist for information regarding interactions for other Unisom products.

1. Other antihistamines

Doxylamine is an antihistamine. So you shouldn’t take it with other oral medications in the same class. Combining doxylamine with other oral antihistamines raises the risk of side effects, such as drowsiness and dry mouth. In severe cases, taking multiple antihistamines at the same time can cause serious side effects, such as a racing heart and balance problems.

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Antihistamines are commonly taken for allergy symptom relief. But they can also help with motion sickness, nausea, and itching. Examples of other antihistamines include:

• Cetirizine (Zyrtec)

• Chlorpheniramine

• Dimenhydrinate (Dramamine)

• Diphenhydramine (Benadryl, Zzzquil, Unisom SleepGels)

• Hydroxyzine (Vistaril)

• Loratadine (Claritin, Alavert)

• Meclizine (Bonine, Dramamine Less Drowsy)

Antihistamines can also be found in combination products, such as menstrual cramp products and cold medications. You should read the OTC label of every product before you take it. If you see an antihistamine listed in the active ingredients section, you shouldn’t take it if you’re already taking doxylamine.

EXPERT PICKS: WHAT TO READ NEXT

• What it feels like: Three people share their experiences with insomnia and how they were able to get the rest they needed.

• Comparing options: Doxylamine is just one example of an OTC sleep medication. Read about other available OTC sleep aids — plus their safety and effectiveness — here.

• Possible side effects: Read about doxylamine’s side effects — from drowsiness to dry mouth — and how to manage them.

2. Other sleeping medications

It’s a good idea to only take one sleeping medication at a time. Combining doxylamine with other sleep aids can lead to excessive drowsiness. And this tiredness could even carry into the next day. This could make driving and other activities that require alertness more dangerous.

Examples of other sleeping medications include:

• Non-benzodiazepine sedative hypnotics (also called “z-drugs”), such as zolpidem (Ambien)

• Melatonin receptor agonists, such as ramelteon (Rozerem)

• Orexin receptor antagonists, such as suvorexant (Belsomra)

• Sleep supplements, such as melatonin

If doxylamine doesn’t seem to be helping you sleep, you should reach out to a healthcare professional (HCP). They may suggest switching medications or trying non-medication techniques. Optimizing your sleep hygiene or practicing yoga nidra could help you get some rest.

3. Opioids

Opioids are prescribed for severe pain when non-opioid pain medications aren’t enough. This class of medications commonly causes drowsiness. You should avoid taking opioids with doxylamine or other medications that cause drowsiness. Taking both can lead to life-threatening exhaustion or slowed breathing.

Doxylamine and opioids share other side effects, such as constipation and dry mouth. These side effects may be worse with the combination than they are when you’re only taking one of them.

Examples of medication that contain opioids include:

• Fentanyl

• Oxycodone (Roxicodone, OxyContin)

• Oxycodone / acetaminophen (Percocet)

• Tramadol (Ultram, ConZip, Qdolo)

If you’re taking an opioid, talk to your prescriber before starting any sleep aids. In general, opioids and sleeping medications don’t mix well. Their combination can cause serious or life-threatening side effects.

4. Benzodiazepines

Benzodiazepines are medications that can treat several conditions including anxiety, seizures, and sleep disorders. They slow down brain activity and can cause drowsiness. Like opioids, it’s not recommended to take doxylamine with benzodiazepines. The combination can lead to dangerous amounts of drowsiness or slowed breathing.

Examples of benzodiazepines include:

• Alprazolam (Xanax)

• Clonazepam (Klonopin)

• Diazepam (Valium)

• Temazepam (Restoril)

You should speak with your prescriber if you’re taking a benzodiazepine and feel like you need a sleep aid. They may make adjustments to your benzodiazepine dosage instead of adding doxylamine. But don’t change the way you’re taking these medications without a healthcare professional’s guidance. Suddenly changing your benzodiazepine dosage could lead to side effects or withdrawal symptoms.

5. Nighttime cold medications

Nighttime cold medications typically contain an antihistamine. This can help with a runny nose and provide a more restful night’s sleep. But taking more than one antihistamine at a time can cause excessive side effects. What’s more, many nighttime cold medications include doxylamine. So taking one of them along with a doxylamine sleep aid would provide too high of a dose.

Common nighttime cold medications that contain an antihistamine include:

• Coricidin HBP Maximum Strength Night Cold and Flu (acetaminophen / dextromethorphan / doxylamine)

• Delsym Nighttime Cough (acetaminophen / dextromethorphan / triprolidine)

• Mucinex Nightshift Cold and Flu (acetaminophen / dextromethorphan / triprolidine)

• NyQuil Cold and Flu (acetaminophen / dextromethorphan / doxylamine)

• Robitussin Maximum Strength Nighttime Cough DM (dextromethorphan / doxylamine)

It’s a good idea to check the active ingredients on the OTC label when purchasing cold medications. But if the product is labeled for nighttime, you should avoid it if you’re already taking doxylamine.

6. Anticholinergic medications

Anticholinergic medications are a broad group of medications. They can treat many health conditions including nausea, irritable bowel syndrome, and overactive bladder. Taking doxylamine with anticholinergic medications can worsen certain side effects. This is because they both block the same chemical in the body.

Anticholinergic medications block the chemical acetylcholine in the body. This action can lead to several side effects. Most notably, these medications can cause dry mouth, constipation, and trouble peeing. While doxylamine isn’t considered an anticholinergic medication, it does have anticholinergic effects. So doxylamine can also cause these same side effects.

A pharmacist is a great resource to tell you if you take an anticholinergic medication. Some common examples include:

• Benztropine

• Dicyclomine

• Mirabegron (Myrbetriq)

• Oxybutynin (Ditropan XL)

• Scopolamine (Transderm Scop)

• Solifenacin (Vesicare)

• Tolterodine (Detrol, Detrol LA)

This combination can be riskier for some people than others. For instance, adults 65 and over shouldn’t take multiple medications with anticholinergic effects. Beyond the above side effects, the combination can also raise the risk of falls for this age group.

Check with a healthcare professional before taking doxylamine with an anticholinergic medication. In some cases, they may give you the OK to take them both and just watch for excess side effects. In others, they may recommend avoiding the combination altogether.

7. Antidepressants

Antidepressants can also interact with doxylamine. Taking these medications together may worsen certain side effects. The most common are dry mouth, drowsiness, and dizziness.

Examples of antidepressants include:

• Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac) and sertraline (Zoloft)

• Serotonin and norepinephrine reuptake inhibitors, such as duloxetine (Cymbalta), venlafaxine (Effexor XR)

• Trazodone

• Tricyclic antidepressants, such as amitriptyline, nortriptyline (Pamelor)

• Monoamine oxidase inhibitors (MAOIs), such as selegiline (Zelapar, Emsam)

It may be OK for some people to take most antidepressants with doxylamine. But it’s best to check with an HCP before taking both. They can weigh your personal risks to let you know if you can combine them.

Good to know: Taking MAOIs with doxylamine is contraindicated. This means that the risk of combining them is greater than the benefits for most people. Combining MAOIs and doxylamine can lead to severe and persistent anticholinergic side effects. Prescribers typically recommend avoiding this combination whenever possible.

8. Muscle relaxers

Muscle relaxers are medications used to treat pain, stiffness, and spasms. Two of the most common side effects of muscle relaxers are dizziness and drowsiness. Some, like cyclobenzaprine (Amrix) and tizanidine (Zanaflex), can also cause anticholinergic side effects. Taking doxylamine with muscle relaxers can worsen these side effects.

Examples of muscle relaxers include:

• Cyclobenzaprine

• Metaxalone

• Methocarbamol (Robaxin)

• Tizanidine

If you take a muscle relaxer, speak with your prescriber before taking doxylamine. Typically, this combination is avoided to prevent complications. But if you only take a muscle relaxer occasionally, you may be able to separate your dose from doxylamine. A healthcare professional can help determine if you can do this safely.

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Written by:

Elizabeth Cambria, PharmD

Elizabeth Cambria is a licensed, registered pharmacist, and certified pharmacist immunizer in the state of Pennsylvania. She graduated with a Doctor of Pharmacy from the University of Pittsburgh School of Pharmacy.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Tegan Smedley, PharmD, APh

Tegan Smedley, PharmD, APh, has 10 years of experience as a pharmacist. She has worked in a variety of settings, including retail, hospital, and ambulatory care.

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